Herbal, extract having therapeutic activity on injuries, and pharmaceutical composition and health food contanining the same

ABSTRACT

The present invention relates to an extract having healing activity on injuries, which is obtained by extracting Astragali Radix, Ginseng Radix, Carthami Flos, Angelicae Gigantis Radix, Cnidii Rhizoma, Rehmanniae Radix Preparata, Paeoniae Radix and Cinnamomi Cortex Spissus with water while heating, and a pharmaceutical composition for treating injuries, a health food for post-surgical recovery and an animal feed containing said extract as the active ingredient.

TECHNICAL FIELD

[0001] The present invention relates to a herbal extract compositionhaving healing activity for injuries, and, more specifically, to theextract composition obtained by extracting Astragali Radix, GinsengRadix, Carthami Flos, Angelicae Gigantis Radix, Cnidii Rhizoma,Rehmanniae Radix Preparata, Paeoniae Radix, and Cinnamomi Cortex Spissuswith water while heating, and to a pharmaceutical composition forhealing injuries, and a health food and an animal feed for post-surgicalrecovery containing said extract as the active ingredient.

BACKGROUND ART

[0002] Bones, flesh, etc. are hurt by injuries, for example, puncturedwound, laceration, wound or fracture, or surgical operations. Manystudies on methods to heal the injuries and to repair the bones andflesh have been continuously made, and thus, a number of healing methodsand agents are known in the Oriental and Western Medicines at thepresent time.

[0003] In the Western medicine, surgical operation techniques have moreadvanced than in the Oriental medicine. Healing agents administeredafter injuries or surgeries, however, do not have very good effects andhave the problem to cause many side effects. For this reason, despiteadministering several wound- or fracture-healing agents to patients withinjuries or surgeries, it is frequently shown that injuries are not wellhealed up, patients are weakened or suffered from severe pain, suture offractured bone is delayed, and side effects like gastric disorders fromhealing agents, e.g. anti-inflammatory drugs, are accompanied.

[0004] In contrast, according to the Chinese medicine, if human beings,who live by Qi·blood·essence of life·vitality, are injured on bones orflesh, skin, subcutaneous fatty layer, flesh and muscle are regenerated,and bones, bone marrow and brain are replenished, and stagnated blood isreplaced with fresh blood, by making Qi·blood·essence of life·vitalityhigher and eliminating extravasated blood to promote vital essence andenergy. Based on this theory, various kinds of healing methods andagents are handed down in the Chinese medical literature. However, ithas been difficult to get satisfactory effects only by such traditionalprescriptions.

DISCLOSURE OF THE INVENTION

[0005] The present inventors referred to many Chinese medical literaturehanded down from ancient times, and conducted many studies andexperiments to develop a healing agent for various injuries,particularly wounds, fractures, etc., or health food for post-surgicalrecovery. As a result, the inventors found that a suitable combinationof specific herbal medicines has excellent healing effects on injuriescompared with other known agents without any toxicity and side effect,and completed the present invention.

[0006] The present invention relates to an extract composition havinghealing activity for injuries, which is obtained by extracting AstragaliRadix, Ginseng Radix, Carthami Flos, Angelicae Gigantis Radix, CnidiiRhizoma, Rehmanniae Radix Preparata, Paeoniae Radix and Cinnamomi CortexSpissus with water while heating.

[0007] The extract composition of the present invention exhibits healingactivity from the above-described herbal medicines for injuries, but tostrengthen its activity, one or more selected from the group consistingof Atractylodis Rhizoma alba, Hoelen, Aurantii Nobilis Pericarpium,Glycyrrhizae Radix, Eucommiae Cortex, Myrrh, Amomi Semen, Walnut,Zingiberis Rhizoma and Zizyphi Fructus are further mixed and the wholemixture is extracted with water while heating.

[0008] As raw herbal medicines essential for the present invention,Astragali Radix has Qi-replenishing, pus-evacuating by administeringtonics, and pain-arresting activities; Ginseng Radix has tonic,stamina-strengthening, calming and fatigue-relieving activities;Carthami Flos enhances functions of bone tissue cells to promote growthof bones; Angclicae Gigantis Radix has blood-replenishing, moistening,calming, analgesic and antibacterial activities; Cnidii Rhizoma hasblood- and Qi-promoting activities; Rehmanniae Radix Preparata hasblood-replenishing, tonic and nourishing activities; Paeoniae Radix hascalming, antispasmodic, antipyretic, analgesic, antibacterial,anti-inflammatory and vasodilating activities; and Cinnamomi CortexSpissus has analgesic and antispasmodic activities.

[0009] As raw herbal medicines which can be further added for thepresent invention, Atractylodis Rhizoma alba has spleen-tonifying andQi-replenishing, dampness-eliminating. and diuresis-inducing, andexterior-reinforcing and sweating-suppressing activities; Hoelen hasstomachic, diuretic and calming activities; Aurantii Nobilis Pericarpiumhas Qi-flow-regulating and spleen-tonifying, stagnation of Qi-removingand phlegni-eliminating, and antiasthmatic and cough-relievingactivities; Glycyrrhizae Radix has cough-relieving, phlegm-eliminating,detoxifying, antispasmodic, anti-inflammatory, analgesic, andanti-hypersensitive activities; Eucornmiae Cortex has tonic,stamina-strengthening, and analgesic activities; Myrrh hasblood-circulation-promoting and pain-arresting activities, andswelling-inducing and Qi-vitalizing activities; Amomi Semen hasspleen-tonifying and Qi-promoting, and spleen-warming and antidiarrhealactivities; Walnut has kidney reinforcing andmuscle-and-bone-strengthening activities; Zingiberis Rhizoma has astomachic activity; and Zizyphi Fructus has tonic, blood-replenishing,laxative, calming, and analgesic activities.

[0010] The composition of the present invention may be preferablyobtained by extracting 4-20 parts of Astragali Radix, 2-12 parts ofGinseng Radix, 2-12 parts of Carthami Flos, 2-12 parts of AngelicaeGigantis Radix, 2-12 parts of Cnidii Rhizoma, 2-12 parts of RehmanniaeRadix Preparata, 2-12 parts of Paeoniae Radix, and 2-12 parts ofCinnamomi Cortex Spissus, wherein all the above parts are based onweights of raw herbal medicines, with water while heating. Morepreferably, the composition is prepared from 8-16 parts of AstragaliRadix, 4-8 parts of Ginseng Radix, 4-8 parts of Carthami Flos, 4-8 partsof Angelicae Gigantis Radix, 4-8 parts of Cnidii Rhizoma, 4-8 parts ofRehmanniae Radix Preparata, 4-8 parts of Paeoniae Radix, and 4-8 partsof Cinnamomi Cortex Spissus, wherein all the above parts are based onweights of raw herbal medicines.

[0011] Also, the composition of the present invention is preferablyprepared by further mixing 2-12 parts of Atractylodis Rhizoma alba, 2-12parts of Hoelen, 2-10 parts of Aurantii Nobilis Pericarpium, 2-12 partsof Glycyrrhizae Radix, 2-18 parts of Eucommiae Cortex, 2-8 parts ofMyrrh, 2-12 parts of Amomi Semen, 4-20 parts of Walnut, 2-10 parts ofZingiberis Rhizoma, and 2-10 parts of Zizyphi Fructus, wherein all theabove parts are based on weights of raw herbal medicines, and extractingthe whole mixture with water while heating. More preferably, thecomposition is prepared by further mixing 4-8 parts of AtractylodisRhizoma alba, 4-8 parts of Hoelen, 3-8 parts of Aurantii NobilisPericarpium, 4-8 parts of Glycyrrhizae Radix, 4-10 parts of EucommiaeCortex, 2-6 parts of Myrrh, 4-8 parts of Amomi Semen, 6-15 parts ofWalnut, 3-8 parts of Zingiberis Rhizoma, and 3-8 parts of ZizyphiFructus, wherein all the above parts are based on weights of raw herbalmedicines.

[0012] The above composition ratios of the herbal medicines are based onthe results of many times of clinical and animal experiments, and, iflower than the lower limits, pharmacological effects of the ingredientsare remarkably decreased, and, if higher than the upper limits,pharmacological effects of other ingredients are decreased to remarkablydeteriorate synergistic and cooperative effects of the composition.

[0013] As shown in the following Experiments 1 and 2, the herbal extractcomposition prepared by the above-described method, has healing activityfor injuries, particularly, wounds or fracture. Therefore, the extractcomposition of the present invention can be used as a healing agent forinjuries such as wounds or fractures, or as a health food or an animalfeed for post-surgical recovery of human beings or animals.

[0014] Therefore, the present invention provides a pharmaceuticalcomposition for healing injuries in human beings or animals comprisingthe above extract composition as the active ingredient. Also, thepresent invention provides a health food or an animal feed forpost-surgical recovery of human beings or animals comprising the aboveextract composition as the active ingredient.

[0015] The composition of the present invention may be prepared in theform of solution, suspension, pill, tablet, capsule or granule bycombining the extract composition obtained by extracting the mixture ofthe above herbal medicines with water while heating, a mixture of theextract obtained by extracting each herbal medicine with a solventdepending upon its physicochemical properties, or powder obtained byconcentrating and drying the extract, with pharmaceutically acceptablecarriers, according to conventional methods. The composition ispreferably prepared in the form of oral solution, suspension or tablet,for good pharmacological effects, but, if necessary, may be prepared inthe form of pill, capsule or granule, and, if necessary, may be changedinto another dosage form before its use.

[0016] For example, the pharmaceutical composition of the presentinvention is prepared by pouring 300 ml of water into the mixture of4-20 g of Astragali Radix, 2-12 g of Ginseng Radix, 2-12 g of CarthamiFlos, 2-12 g of Angelicae Gigantis Radix, 2-12 g of Cnidii Rhizoma, 2-12g of Rehmanniae Radix Preparata, 2-12 g of Paeoniae Radix and 2-12 g ofCinnamomi Cortex Spissus, and optionally, one or more selected from thegroups consisting of 2-12 g of Atractylodis Rhizoma alba, 2-12 g ofHoelen, 2-10 g of Aurantii Nobilis Pericarpium, 2-12 g of GlycyrrhizaeRadix, 2-18 g of Eucommiae Cortex, 2-8 g of Myrrh, 2-12 g of AmomiSemen, 4-20 g of Walnut, 2-10 g of Zingiberis Rhizoma, and 2-10 g ofZizyphi Fructus, extracting the whole mixture while heating for about 2hours, filtering the extract, and concentrating the filtrate to 120 mlor freeze-drying it.

[0017] A single dose of the present composition is usually in the rangeof 0.1 to 30 g as freeze-dried powder for an adult, and it is taken onceto three times a day. However, a dosage of the composition of thepresent invention may be suitably changed depending upon a patient'sbody weight, age, sexuality, severity of disease, and digestibility.Other formulations may also be taken at suitable dosages.

BRIEF DESCRIPTION OF THE DRAWINGS

[0018]FIG. 1 is a photograph of a rat in which skin wounds are induced;

[0019] FIGS. 2 to 7 are photographs showing the wounded sites afterorally administering 0 mg/kg (control), 50 mg/kg (low-dosage group), and200 mg/kg (high-dosage group) of the present composition for 7 and 14days, respectively;

[0020]FIG. 8 is a graph showing changes in body weights of rats incontrol and experimental groups;

[0021] FIGS. 9 to 14 are optical micrographs showing the H&E-stainedwound tissues in control and experimental groups;

[0022]FIG. 15 is a graph showing changes in body weights after orallyadministering 0 mg/kg (control), 50 mg/kg (first group), and 100 mg/kg(second group) of the present composition for 6 weeks, respectively;

[0023] FIGS. 16 to 25 are radiographs of the fractured sites in controland first group;

[0024]FIG. 26 is a graph showing the endurance time in a rota-rod testafter administering the present composition for 5 weeks;

[0025] FIGS. 27 to 29 are photographs showing the gross examinationresults of the extracted tibia and fibula in control, first, and secondgroups; and,

[0026] FIGS. 30 to 32 are photographs showing the examination results ofthe fibular tissues in control, first, and second groups.

BEST MODE FOR CARRYING OUT THE INVENTION

[0027] Hereinafter, this invention will be more specifically explainedwith reference to examples, but they should not be construed to limitthe present invention in any manner.

EXAMPLE 1 Preparation of Solution and Freeze-Dried Powder

[0028] Into a mixture of 80 g of Astragali Radix, 60 g of Ginseng Radix,60 g of Carthami Flos, 50 g of Angelicae Gigantis Radix, 50 g of CnidiiRhizoma, 50 g of Rehmanniae Radix Preparata, 50 g of Paeoniae Radix, 50g of Cinnamomi Cortex Spissus, 50 g of Atractylodis Rhizoma alba, 50 gof Hoelen, 50 g of Aurantii Nobilis Pericarpium, 60 g of GlycyrrhizaeRadix, 60 g of Eucommiae Cortex, 20 g of Myrrh, 40 g of Amomi Semen, 60g of Walnut, 40 g of Zingiberis Rhizoma, and 40 g of Zizyphi Fructus waspoured 2000 ml of water. The whole mixture was extracted while heatingfor about 2 hours and filtered, and then, the filtrate was concentratedto 900 ml. Then, the concentrate was freeze-dried to obtain 110 g of thepowdered extract.

EXAMPLE 2 Preparation of Other Formulations

[0029] According to conventional methods, pills, granules, sprays,tablets, and capsules were prepared using the extract composition or itsconcentrated dried powder obtained from the above Example 1.

Experiment 1: Evaluation of Wound-Healing Effect

[0030] The composition of the present invention, which was orallyadministered, was tested for its healing effect on full-thickness skinwound induced in the dorsal area of rats.

[0031] Three square skin wounds, each of which had the size of 1 cm×1cm, were induced in the dorsal side of fifteen male rats with the age of10 weeks.

[0032] For trial groups, the composition obtained from the above Example1 was orally administered to the rats at 200 mg/kg body weight(high-dosage group), 50 mg/kg body weight (low-dosage group), and 0mg/kg body weight (control group) once a day for 14 days, respectively,and degrees of contraction, re-epithelialization, and healing of woundwere histopathologically examined with the naked eyes.

[0033] As a result, at 7 days after inducing wounds, degrees ofcontraction and healing of wound were observed to be higher in thehigh-dosage group (FIG. 4) than in the control group (FIG. 2), anddegree of wound healing was high on both ends in the case of thelow-dosage group (FIG. 3). At 14 days after inducing wounds, a morenoticeable healing effect was observed in the high-dosage group (FIG. 7)than in the control group (FIG. 5), and the higher healing effect wasalso observed in the low-dosage group (FIG. 6) than in the controlgroup, even though it was lower than in the high-dosage group. Forchanges of body weights for 14 days, it was observed that body weightsslightly decreased because of stress and pain after inducing wounds, butthere was no significant difference in body weights between the groupsduring the whole experiments (FIG. 8).

[0034] At 14 days after inducing wounds, the wound tissues in thecontrol and experimental groups were made into specimens and thespecimens were stained with H&E and observed under an opticalmicroscope. In the control group (FIGS. 9 and 10), thin epitheliallayer, sparse tissue texture, and low distribution of vessels wereobserved. On the contrary, in the low-dosage group (FIGS. 11 and 12),thicker epithelial layer and denser tissue texture than the controlgroup were observed. In the high-dosage group, smoother epithelialsurface than in other groups, slowly curved epithelial layer, and sweatgland and hair follicles were observed (FIGS. 13 and 14). Usually, sweatgland and hair follicles could be observed at 28 days after injury, buthair follicles could be observed in most high-dosage groups and somelow-dosage groups, which means that the wound healing effect of thecomposition of the present invention was very fast. Therefore, thepresent composition was demonstrated to have a fast wound healing effectupon oral administration.

Experiment 2: Evaluation of Fracture-Healing Effect

[0035] 1. Healing Process of Bone Fracture

[0036] The healing process of bone fracture is a very complex oneincluding normal wound healing processes, which leads to restoration oforiginal integrity and strength which can stand against the loading ofskeleton through normal physiological processes. The healing processesof bone fracture may be divided into the following three phases:

[0037] First phase: Inflammatory phase wherein an inflammatory reactionis triggered by formation of hematoma that is a mass of blood clot fromblood leaked out of injured vessels in a fractured area, followed byacute edema;

[0038] Second phase: Reconstructive phase wherein fibroblastproliferation and granulation tissue formation with angiogenesis inducetissue organization, which leads to progressive endochondralossification through formation of cartilage and callus (immature bonetissue) around fractured sites; and,

[0039] Third phase: Remodeling phase wherein a newly formed callus isgradually replaced by a mature lamellar bone and an excessively formedbone is absorbed by osteoclasts.

[0040] In this experiment, in order to examine a fracture-healing effectof the composition of the present invention, the healing index of bonefracture was evaluated with a bone fracture model in rats.

[0041] 2. Methods

[0042] After the fibular fracture was surgically induced in rats, thecomposition obtained from Example 1 was administered with changing dosesfor six weeks.

[0043] That is, after fifteen adult male rats (318±40 g) wereintraperitoneally injected with 15 mg/100 of ketamine HCl to inducegeneral anesthesia, the rat's hairs were shaven in the right hind legwith an electric clipper, and the rats were laid on the left side, anddisinfected at the surgical area with povidon-iodine and alcohol. Afterskin incision, anterior tibia muscle and gastrocnemius muscle weredissected bluntly and the fibula was exposed. The exposed fibula wasforced with a clamp to induce the transverse fracture. Then, the fifteenrats with fibular fracture were divided into three groups, five rats pergroup, and the composition of the present invention was orallyadministered at 100 mg/kg body weight (1st group), 50 mg/kg body weight(2nd group) and 0 mg/kg body weight (control group) as the freeze-driedpowder, respectively.

[0044] The healing process of bone fracture was radiologically examinedat 1, 2, 3, 4 and 5 weeks after inducing bone fracture, and, at thefinal week, the locomotion amount was measured and compared between thegroups by performing the rota-rod test at 8 rpm, and the rats wereautopsied for the subsequent histopathological examination.

[0045] 3. Results

[0046] As an index of fracture healing effect, gross examination,radiography, histomorphological examination of callus, and rota-rod testfor tissues of the fractured sites were performed.

[0047] (1) Changes in Body Weights

[0048] Body weights were measured once a week, and during the wholeexperiments, there was no significant difference in body weightscompared with the control group (FIG. 15).

[0049] (2) Radiological Examination

[0050] Radiographs were taken at 1, 2, 3, 4, and 5 weeks after inducingbone fracture to observe healing of the right fibular fracture. Theresults are shown in FIGS. 16 to 25.

[0051] Radiographs taken at one week after fracture did not show anysignificant difference between control and drug administered groups(FIGS. 16 and 21). On radiographs taken at 3 weeks after fracture,however, significant differences were shown between the groups and theywere in proportion to administered doses. The healing speed in the firstgroup was faster than that in control group by about one week and thehealing speed in the second group was about as half fast as that in thefirst group. On the final radiograph taken at 5 weeks after fracture,complete calcification was observed in the first group (FIG. 25), whileonly callus formation and incomplete calcification were observed in thecontrol group (FIG. 20).

[0052] (3) Rota-Rod Test

[0053] In order to indirectly examine the degree of fracture healing inthe trial groups before autopsy at 5 weeks, locomotion ability wasevaluated. Individual animals in all the trial groups were placed on arota-rod and the endurance time was measured, and the results are shownin FIG. 26. It shows that the first group had the longest endurancetime.

[0054] (4) Gross Examination After Extraction of Bone

[0055] The extracted tibia and fibula from autopsies were examined withthe naked eyes. Healing process seemed to be in remodeling phase aftercompleting the formation of callus in the low-dosage group (FIG. 28) andthe final step of remodeling phase in the high-dosage group (FIG. 29),while the callus was actively formed in the control group at five weeks(FIG. 27).

[0056] (5) Histopathological Examination

[0057] A histopathological examination was performed after decalcifyingthe extracted fibula and making specimen. Ossification seemed toprogress by mineral deposition in the low-dosage group (FIG. 31) andrestoration of normal bone tissues by reconstruction (remodeling) wasobserved in the high-dosage group (FIG. 32), while only the callus wasformed and lacunar structures were clearly observed in the control group(FIG. 30).

[0058] 4. Conclusion

[0059] From the above results, the composition of the present inventionwas concluded to have a fast healing effect on bone fracture upon oraladministration.

Industrial Applicability

[0060] As can be seen from the above experiments, the extractcomposition of the present invention having the healing effect forinjuries, particularly, wound or bone fracture is extremely useful as apharmaceutical composition for healing injuries, or a health food or ananimal feed for post-surgical recovery of human beings or animals.

What is claimed is:
 1. An extract composition having healing activityfor injuries, prepared by extracting Astragali Radix, Ginseng Radix,Carthami Flos, Angelicae Gigantis Radix, Cnidii Rhizoma, RehmanniaeRadix Preparata, Paeoniae Radix and Cinnamomi Cortex Spissus with waterwhile heating.
 2. The extract composition of claim 1, prepared byfurther mixing one or more herbal medicines selected from the groupconsisting of Atractylodis Rhizoma alba, Hoelen, Aurantii NobilisPericarpium, Glycyrrhizae Radix, Eucommiae Cortex, Myrrh, Amomi Semen,Walnut, Zingiberis Rhizoma, and Zizyphi Fructus, and extracting thewhole mixture with water while heating.
 3. The extract composition ofclaim 1, wherein the weight ratio of Astragali Radix, Ginseng Radix,Carthami Flos, Angelicae Gigantis Radix, Cnidii Rhizoma, RehmanniaeRadix Preparata, Paeoniae Radix, and Cinnamomi Cortex Spissus is 4-20:2-12: 2-12: 2-12: 2-12: 2-12: 2-12: 2-12.
 4. The extract composition ofclaim 3, wherein the weight ratio of Astragali Radix, Ginseng Radix,Carthami Flos, Angelicae Gigantis Radix, Cnidii Rhizoma, RehmanniaeRadix Preparata, Paeoniae Radix and Cinnamomi Cortex Spissus is 8-16:4-8: 4-8: 4-8: 4-8: 4-8: 4-8: 4-8.
 5. The extract composition of claim3, prepared by further mixing one or more herbal medicines selected fromthe group consisting of 2-12 parts of Atractylodis Rhizoma alba, 2-12parts of Hoelen, 2-10 parts of Aurantii Nobilis Pericarpium, 2-12 partsof Glycyrrhizae Radix, 2-18 parts of Eucommiae Cortex, 2-8 parts ofMyrrh, 2-12 parts of Amomi Semen, 4-20 parts of Walnut, 2-10 parts ofZingiberis Rhizoma, and 2-10 parts of Zizyphi Fructus, and extractingthe whole mixture with water while heating.
 6. The extract compositionof claim 5, prepared by further mixing one or more herbal medicinesselected from the group consisting of 4-8 parts of Atractylodis Rhizomaalba, 4-8 parts of Hoelen, 3-8 parts of Aurantii Nobilis Pericarpium,4-8 parts of Glycyrrhizae Radix, 4-10 parts of Eucommiae Cortex, 2-6parts of Myrrh, 4-8 parts of Amomi Semen, 6-15 parts of Walnut, 3-8parts of Zingiberis Rhizoma, and 3-8 parts of Zizyphi Fructus, andextracting the whole mixture with water while heating.
 7. Apharmaceutical composition for healing injuries in human beings oranimals, containing the extract composition of any one of claims 1 to 6as the active ingredient.
 8. A health food or an animal feed forpost-surgical recovery, containing the extract composition of any one ofclaims 1 to 6 as the active ingredient.
 9. The composition, or healthfood or animal feed of claim 7 or 8, which is in the form of solution,suspension, tablet, pill, capsule or granule.